Association between a glutathione S‐transferase A1 promoter polymorphism and survival after breast cancer treatment
Open Access
- 6 December 2002
- journal article
- research article
- Published by Wiley in International Journal of Cancer
- Vol. 103 (6), 810-814
- https://doi.org/10.1002/ijc.10896
Abstract
Glutathione S-transferase (GST) enzymes detoxify chemotherapeutic drugs, and several studies have reported differences in survival for cancer patients who have variant genotypes for GSTP1, GSTM1 or GSTT1 enzymes. A recently described polymorphism alters hepatic expression of GSTA1, a GST with high activity in glutathione conjugation of metabolites of cyclophosphamide (CP). To consider the possible influence of the reduced-expression GSTA1*B allele on cancer patient survival, we have conducted a pilot study of breast cancer patients treated with CP-containing combination chemotherapy. GSTA1 genotype was determined by polymerase chain reaction and restriction fragment length polymorphism. Kaplan-Meier methods and Cox proportional hazards models were used to evaluate survival in relation to genotype. Among 245 subjects, 35% were GSTA1*A/*A, 49% GSTA1*A/*B and 16% GSTA1*B/*B; the genotype distribution did not differ by ethnic group, age or stage at diagnosis. Among patients who had 0 or 1 GSTA1*B allele, the proportion surviving at 5 years was 0.66 (95% CI = 0.59–0.72), whereas for GSTA1*B/*B subjects the proportion was higher, 0.86 (95% CI = 0.67–0.95). Significantly reduced hazard of death was observed for GSTA1*B/*B subjects during the first 5 years after diagnosis, hazard ratio (HR) = 0.3, 95% CI = 0.1–0.8. The association varied with time, with no survival difference observed for subjects who survived beyond 5 years. These results, although based on a small study population, describe an apparent difference in survival after treatment for breast cancer according to GSTA1 genotype. Further studies should consider the possible association between the novel GSTA1*B variant and outcomes of cancer therapy.Keywords
This publication has 18 references indexed in Scilit:
- Association Between Glutathione S-Transferase P1, T1, and M1 Genetic Polymorphism and Survival of Patients With Metastatic Colorectal CancerJNCI Journal of the National Cancer Institute, 2002
- Ligandin revisited: resolution of the alpha class glutathione transferase gene familyPharmacogenetics, 2002
- Progress in systemic chemotherapy of primary breast cancer: an overview.JNCI Monographs, 2001
- Polymorphism in glutathione S -transferase P1 is associated with susceptibility to chemotherapy-induced leukemiaProceedings of the National Academy of Sciences of the United States of America, 2001
- Polychemotherapy for early breast cancer: an overview of the randomised trialsThe Lancet, 1998
- Dose and Dose Intensity as Determinants of Outcome in the Adjuvant Treatment of Breast CancerJNCI Journal of the National Cancer Institute, 1998
- Glutathione Conjugation of Alkylating Cytostatic Drugs with a Nitrogen Mustard Group and the Role of Glutathione S-TransferasesChemical Research in Toxicology, 1996
- Adjuvant Cyclophosphamide, Methotrexate, and Fluorouracil in Node-Positive Breast Cancer — The Results of 20 Years of Follow-upNew England Journal of Medicine, 1995
- The Glut athione S-Transferase Supergene Family: Regulation of GST and the Contribution of the lsoenzymes to Cancer Chemoprotection and Drug Resistance Part ICritical Reviews in Biochemistry and Molecular Biology, 1995
- Quantification of human hepatic glutathione S-transferasesBiochemical Journal, 1990